rs601338

Variant names:

• chr19-48703417-G-A
• rs601338
• NM_000511.6:c.461G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000511.6(FUT2):​c.461G>A​(p.Trp154*) variant causes a stop gained change. The variant allele was found at a frequency of 0.458 in 1,612,604 control chromosomes in the GnomAD database, including 179,977 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15740 hom., cov: 32)
  • Exomes 𝑓: 0.46 (164237 hom.)
• Consequence: FUT2 NM_000511.6 stop_gained
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:2
• Conservation: PhyloP100: 4.26
• Publications: 393 publications found

Genes affected

FUT2 (HGNC:4013): (fucosyltransferase 2 (H blood group)) This gene is one of two encoding the galactoside 2-L-fucosyltransferase enzyme. The encoded protein is important for the final step in the soluble ABO blood group antigen synthesis pathway. It is also involved in cell-cell interaction, cell surface expression, and cell proliferation. Mutations in this gene are a cause of the H-Bombay blood group where red blood cells lack the H antigen. [provided by RefSeq, May 2022]

LOC105447645 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 19-48703417-G-A is Benign according to our data. Variant chr19-48703417-G-A is described in ClinVar as Benign. ClinVar VariationId is 12945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000511.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT2	NM_000511.6	MANE Select	c.461G>A	p.Trp154*	stop_gained	Exon 2 of 2	NP_000502.4	A8K2L2
	FUT2	NM_001097638.3		c.461G>A	p.Trp154*	stop_gained	Exon 2 of 2	NP_001091107.1	Q10981
	LOC105447645	NR_131188.1		n.432C>T		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT2	ENST00000425340.3	TSL:1 MANE Select	c.461G>A	p.Trp154*	stop_gained	Exon 2 of 2	ENSP00000387498.2	Q10981
	FUT2	ENST00000522966.2	TSL:2	c.461G>A	p.Trp154*	stop_gained	Exon 2 of 2	ENSP00000430227.2	Q10981
	FUT2	ENST00000960751.1		c.461G>A	p.Trp154*	stop_gained	Exon 3 of 3	ENSP00000630810.1

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66996 AN: 151762 Hom.: 15747 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.00386

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.458

GnomAD2 exomes AF: 0.383 AC: 95772 AN: 250156 AF XY: 0.387

Gnomad AFR exome AF: 0.498

Gnomad AMR exome AF: 0.265

Gnomad ASJ exome AF: 0.451

Gnomad EAS exome AF: 0.00224

Gnomad FIN exome AF: 0.374

Gnomad NFE exome AF: 0.476

Gnomad OTH exome AF: 0.431

GnomAD4 exome AF: 0.460 AC: 671929 AN: 1460728 Hom.: 164237 Cov.: 75 AF XY: 0.455 AC XY: 330704 AN XY: 726622

African (AFR) AF: 0.500 AC: 16743 AN: 33480

American (AMR) AF: 0.277 AC: 12385 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 11661 AN: 26136

East Asian (EAS) AF: 0.00159 AC: 63 AN: 39668

South Asian (SAS) AF: 0.320 AC: 27501 AN: 85890

European-Finnish (FIN) AF: 0.376 AC: 19850 AN: 52738

Middle Eastern (MID) AF: 0.515 AC: 2968 AN: 5764

European-Non Finnish (NFE) AF: 0.497 AC: 552819 AN: 1111986

Other (OTH) AF: 0.463 AC: 27939 AN: 60344

GnomAD4 genome AF: 0.441 AC: 67000 AN: 151876 Hom.: 15740 Cov.: 32 AF XY: 0.429 AC XY: 31842 AN XY: 74210

African (AFR) AF: 0.499 AC: 20657 AN: 41430

American (AMR) AF: 0.368 AC: 5615 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1541 AN: 3472

East Asian (EAS) AF: 0.00387 AC: 20 AN: 5168

South Asian (SAS) AF: 0.295 AC: 1399 AN: 4736

European-Finnish (FIN) AF: 0.368 AC: 3893 AN: 10590

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32438 AN: 67924

Other (OTH) AF: 0.452 AC: 954 AN: 2112

Alfa AF: 0.472 Hom.: 21059

Bravo AF: 0.445

TwinsUK AF: 0.494 AC: 1830

ALSPAC AF: 0.499 AC: 1924

ESP6500AA AF: 0.496 AC: 2186

ESP6500EA AF: 0.492 AC: 4231

ExAC AF: 0.389 AC: 47143

Asia WGS AF: 0.141 AC: 490 AN: 3414

EpiCase AF: 0.480

EpiControl AF: 0.480

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Bombay phenotype;C2674252:VITAMIN B12 PLASMA LEVEL QUANTITATIVE TRAIT LOCUS 1 (1)
-	-	1	not provided (1)
-	-	1	SECRETOR/NONSECRETOR POLYMORPHISM (1)
-	-	-	Familial Otitis Media (1)
-	-	-	VITAMIN B12 PLASMA LEVEL QUANTITATIVE TRAIT LOCUS 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Pathogenic	0.60
CADD	Pathogenic	46
DANN	Uncertain	1.0
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.89	D
PhyloP100		4.3
Vest4		0.70
GERP RS		4.8
Mutation Taster		=111/89	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs601338; hg19: chr19-49206674; COSMIC: COSV67178879;